Linh Nguyen Thi Thuy, Giang Nguyen Hoang, Lien Nguyen Thi Kim, Trang Bui Kieu, Trang Do Thi, Ngoc Nguyen Thy, Nghia Vu Xuan, My Le Tra, Mao Can Van, Hoang Nguyen Huy, Xuan Nguyen Thi
University of Science and Technology, Vietnam Academy of Science and Technology, Ha Noi, Vietnam.
Institute of Genome Research, Vietnam Academy of Science and Technology, Ha Noi, Vietnam.
Genet Mol Biol. 2022 Nov 7;45(4):e20220099. doi: 10.1590/1678-4685-GMB-2022-0099. eCollection 2022.
Psoriasis is a common chronic, immune-mediated inflammatory disease of the skin. PSORS1C3 is a non-protein coding gene, of which the RNA transcript is found in psoriatic patients. CARD14 is mainly expressed in epidermal keratinocytes. TLR4 is a transmembrane protein to recognize microbial antigens. Our study aimed to assess the relationship among PSORS1C3, CARD14 and TLR4 polymorphisms, inflammatory expression and psoriasis susceptibility. To the end, 71 patients with psoriasis and 46 healthy individuals with the well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by Sanger DNA sequencing and secretion of cytokines by ELISA. As a result, genetic analysis of PSORS1C3 gene identified nine SNPs and three haplotype blocks. Sequencing of the CARD14 gene determined eight SNPs and one haplotype block. Sequencing of TLR4 gene identified nine SNPs, in which a SNP rs1018673641 was found to exert deleterious effect. The linkage disequilibrium analysis showed that seven variants in PSORS1C3 gene and three SNPs in CARD14 gene were in tightly linked. More importantly, a significant association between IL-6 level and rs1018673641 AT genotype in TLR4 gene was detected in psoriatic patients. In conclusion, the PSORS1C3, CARD14 and TLR4 polymorphisms and haplotypes may be correlated with risk of suffering psoriasis and the IL-6-mediated chronic inflammation in psoriasis could be partially regulated by the TLR4 functional variant.
银屑病是一种常见的慢性、免疫介导的皮肤炎症性疾病。PSORS1C3是一个非蛋白质编码基因，其RNA转录本在银屑病患者中被发现。CARD14主要在表皮角质形成细胞中表达。TLR4是一种识别微生物抗原的跨膜蛋白。我们的研究旨在评估PSORS1C3、CARD14和TLR4基因多态性、炎症表达与银屑病易感性之间的关系。为此，招募了71例银屑病患者和46例具有明确临床特征的健康个体。通过桑格DNA测序确定基因多态性，并通过酶联免疫吸附测定法检测细胞因子的分泌。结果，PSORS1C3基因的遗传分析鉴定出9个单核苷酸多态性（SNP）和3个单倍型块。CARD14基因测序确定了8个SNP和1个单倍型块。TLR4基因测序鉴定出9个SNP，其中一个SNP rs1018673641被发现具有有害作用。连锁不平衡分析表明，PSORS1C3基因中的7个变异和CARD14基因中的3个SNP紧密连锁。更重要的是，在银屑病患者中检测到TLR4基因中IL-6水平与rs1018673641 AT基因型之间存在显著关联。总之，PSORS1C3、CARD14和TLR4基因多态性和单倍型可能与患银屑病的风险相关，并且银屑病中IL-6介导的慢性炎症可能部分受TLR4功能变异的调节。
